Effects of nitroglycerin and nitroprusside on the uterine vasculature of gravid ewes

The effects of nitroglycerin (TNG) and sodium nitroprusside (SNP) on mean aortic pressure (MAP), uterine blood flow (UBF), uterine vascular conductance (UVC), and pulse rate (PR) were compared when the two agents were infused to prevent and treat hypertension induced by norepinephrine (NE) in gravid ewes. When infused alone, TNG, 19 microgram/kg/min, decreased MAP 19 per cent and increased PR 33 per cent from control values (P less than 0.05), but did not significantly change UBF or UVC. In comparison, SNP, 3 microgram/kg/min, decreased MAP 20 per cent and increased PR 43 per cent (P less than 0.05), and did not significantly change UBF or UVC. When given alone, four successive 2-min infusions of NE produced dose-related increase in MAP and decreases in UBF, UVC, and PR; values were significantly different from control with the two higher doses of NE. Although MAP, UBF, and UVC were still significantly changed from control levels when NE was given in the presence of the above infusions of TNG or SNP, MAP was lower and UBF and UVC were higher compared with when NE was given alone (P less than 0.05). When given to control hypertension induced by a continuous infusion of NE, TNG or SNP produced uterine vasodilatation and significantly increased UBF. Nitroglycerin and SNP were equally effective in counteracting the maternal hypertension and antagonizing the uterine vascular effect of NE. It is concluded that TNG and SNP counteract uterine vasoconstriction resulting from alpha-adrenergic stimulation and do not produce a shunt of blood flow away from the uterine vasculature when used to control hypertension in gravid ewes.     

The influence of alfentanil pre-treatment on ventilatory effects of doxapram following induction of anaesthesia with propofol

Background : Hypoventilation may occur following induction of anaesthesia with propofol and is potentiated by concurrent use of opioid drugs. This effect is undesirable in patients who will continue to maintain spontaneous respiration during anaesthesia and surgery. The analeptic drug doxapram is known to have selective respiratory stimulatory effects but its action during induction of anaesthesia has been inconsistent.
Method : In a double-blind, placebo-controlled study, the influence of alfentanil pre-treatment on the ventilatory effects of doxapram given during induction of anaesthesia with propofol was studied in 40 patients. Four groups of ten patients (two groups pre-treated with 7 μg·kg^-1 of alfentanil and two groups with saline) were randomly allocated to receive either 0.5 mg·kg^-1doxapram or saline following infusion of propofol to loss of verbal contact.
Results : In the groups that received doxapram, minute volumes were significantly increased and end-tidal carbon dioxide concentrations were significantly reduced compared to control groups, although the duration and extent of these effects were less in the group that received alfentanil. Doxapram also reversed an alfentanil-induced reduction in respiratory rate. No adverse cardiovascular or neurological stimulatory effects of doxapram were evident at any time.
Conclusion : We conclude that doxapram 0.5 mg·kg^-1 is effective in augmenting ventilation that has been obtunded following induction of anaesthesia with propofol in patients pre-treated with alfentanil.     

The comparative effect of single dose mivacurium during sevoflurane or propofol anesthesia in children

BACKGROUND: We aimed to randomly compare intubating conditions, recovery characteristics and neuromuscular effects of single dose of mivacurium (0.2 mg.kg(-1)) during sevoflurane vs. propofol anesthesia in 60 healthy children, undergoing inguinal surgery. METHODS: All children were randomly allocated to receive 2 mg.kg(-1) propofol iv or sevoflurane 8% inspired concentration for induction of anesthesia. Anaesthesia was maintained with 66% nitrous oxide in oxygen and 100-120 microg.kg(-1) propofol or sevoflurane approximately 2-3% inspired concentration with controlled ventilation. The ulnar nerve was stimulated at the wrist by a train-of four (TOF) stimulus every 20 s and neuromuscular function was measured at the adductor pollicis. When the response to TOF was stable, 0.2 mg.kg(-1) mivacurium was given. The trachea was intubated successfully at the first attempt in all patients. RESULTS: Onset time following a single dose of mivacurium was shorter in the sevoflurane group (2.99 min), than in the propofol group (4.42 min). The times to 25, 50, 75, and 90% recovery were significantly longer in the sevoflurane group (13.1, 15.7, 18.6, and 21.2 min, respectively) than in the propofol group (11.4, 13.2, 14.4, and 17.2 min respectively). TOF ratios of 50, 70, and 90% were significantly occurred later in sevoflurane group than propofol group. CONCLUSIONS: Our results indicate that when compared with propofol group, the sevoflurane group had an accelerated onset and a delayed recovery of neuromuscular block induced by mivacurium in children.     

Effects of different preparations of propofol, diazepam, and etomidate on human neutrophils in vitro

BACKGROUND: Intravenous anaesthetics and sedatives can influence polymorphonuclear cell (PMN) functions. Some of the drugs for sedation and anaesthesia have been alternatively dissolved in lipid solutions containing medium (MCT) and/or long chain (LCT) triglycerides. The in vitro effects of two different diazepam (benzyl-alcohol, LCT/MCT), etomidate (propylene-glycol, LCT/MCT), and propofol (LCT, LCT/MCT) preparations on respiratory burst (RB) and phagocytosis of human PMNs were studied. METHODS: Diazepam (2, 20 microg ml(-1)), etomidate (0.5, 5 microg ml(-1)), and propofol (6, 60 microg ml(-1)) were investigated in clinical and 10-fold concentrations with flow cytometric assays. The RB was measured with the fluorescent dye rhodamine after induction with Escherichia coli or formyl-methionyl-leucylphenylalanine (FMLP) following priming with tumour necrosis factor alpha (TNF-alpha). Phagocytosis of PMNs was carried out in whole blood after incubation with fluorescein-labelled E. coli. RESULTS: LCT-propofol at 60 microg ml(-1) reduced the percentage of PMNs with RB activity after induction with E. coli (52.8+/-20.4) and TNF-alpha/FMLP (10.8+/-5.1)) as well as the percentage of phagocytosing PMNs (48.9+/-19.5) in contrast to LCT/MCT-propofol, which augmented all parameters (85.4+/-10.1, 50.3+/-12.7, 66.5+/-12.5). Also the higher concentrations of LCT/MCT-diluted etomidate and diazepam increased the percentage of RB positive PMNs compared to the alternative compositions. The percentage of phagocytosing PMNs was less reduced with 20 microg ml(-1) LCT/MCT-diazepam (85.2+/-6.9) than with the same concentration of benzyl-alcohol diluted diazepam (68.8+/-12.2) compared to the control. CONCLUSION: The in vitro effects of diazepam, etomidate, and propofol are dependent on the solvent applied. The tested LCT/MCT preparations reduce the inhibitory effects on the bacterial killing capacity of PMNs found after incubation with propyleneglycol, benzyl-alcohol, or LCT preparations, respectively.     

Effects of propofol and thiopentone on polymorphonuclear leukocyte functions in vitro

Anaesthetic agents may impair host defense mechanisms including polymorphonuclear leukocyte (PMNL) function.
We have studied the effects of thiopentone and propofol in low (thiopentone 10 mg/L, propofol 2 mg/1) and high (thiopentone 40 mg/L, propofol 6 mg/L) clinically relevant concentrations on PMNL adherence, chemotaxis, phagocytosis and killing in vitro.
The results demonstrated that thiopentone in both concentrations significantly decreases all PMNL functions tested and had a direct influence on the PMNLs in terms of their chemotactic response. In contrast, propofol decreases significantly only PMNL chemotaxis but not adherence, phagocytosis and killing. The effect of propofol was not attributable to the lipid carrier vehicle, as Intralipid with same formulation had no effect on PMNL function.     

Tracheal intubation after induction of anaesthesia with thiopentone or propofol without muscle relaxants

This study was designed to compare the ease of performing laryngoscopy and endotracheal intubation without muscle relaxants after the induction of anaesthesia with either thiopentone or propofol in 106 patients scheduled for elective surgery. Thiopentone (5 mg/kg) or propofol (2.5 mg/kg), supplemented with lidocaine (1.5 mg/kg) and alfentanil (30 micrograms/kg), were used in random order for the induction of anaesthesia. Jaw tone, visualisation of the larynx, position of vocal cords, ease of intubation and tolerance of the tracheal tube were assessed. The jaw was relaxed and the vocal cords were immobile/open in most patients in both groups. Visualisation of the larynx was good in 60 and 46% and intubation was easy in 48 and 22% of the patients given thiopentone and propofol, respectively (P less than 0.05 between groups for intubation). After induction of anaesthesia with thiopentone or propofol, endotracheal intubation is not recommended without the use of muscle relaxants.     

Effects of propofol and thiopental on the central nervous system during nociceptive stimulation in cats

Purpose. Nociceptive stimulation may increase central nervous system (CNS) activity during anesthesia. However, it is not known whether propofol and thiopental have a similar inhibitory effect on the CNS during nociceptive stimulation. Therefore, we compared the antinociceptive effects of propofol and thiopental in cats. Methods. In 12 cats, anesthesia was induced with 4% halothane in oxygen and maintained with 0.5% halothane in oxygen. The cortical electroencephalogram (EEG) and the electrical activity from the midbrain reticular neurons (R-MUA) were measured before and after sciatic nerve stimulation. The cats were then allocated to receive cumulative doses of either propofol (n = 6) or thiopental (n = 6) i.v. at 5-min intervals. Two minutes after each dose, the cortical EEG and the R-MUA were compared before and after sciatic nerve stimulation. Results. Propofol and thiopental depressed the basal R-MUA to a similar degree at each dose. Sciatic nerve stimulation increased the R-MUA, and there were no differences in the maximum R-MUA values between propofol and thiopental. The cortical EEGs after each dose of anesthetic without stimulation showed similar patterns, and the patterns of change with stimulation were also similar for these two anesthetics. Conclusion. Propofol and thiopental have similar antinociceptive effects in cats. Received: October 10, 2000 / Accepted: April 2, 2001     

Effects of bupivacaine and calcium antagonists on the rat uterine artery

Bupivacaine is a commonly used local anesthetic in obstetrical practice, but since this compound also has a constrictor action on vascular smooth muscle it can be hazardous to the fetus. The aim of the present study was to analyze the effect of bupivacaine on the uterine vasculature using the rat uterine artery as a model. Small arterial segments were mounted in tissue chambers for isometric recording of vascular tension using a specially designed teflon-steel gauge. Bupivacaine induced marked vasoconstriction and this vasoconstriction was reduced considerably by two different Ca antagonists, verapamil and nifedipine. Verapamil (10(-5) mol.l-1) reduced bupivacaine-produced arterial contraction by a mean of 78% and nifedipine (2.9 x 10(-7) mol.l-1) reduced arterial contraction by a mean of 57%.     

Effects of local anesthetics on human bladder contractility

AIMS: We investigated the invitro effects of local anesthetics on the contractility of the human bladder. METHODS: By measuring the invitro isometric contractions of human bladder strips, we determined the effects of tetracaine, bupivacaine, lidocaine, and ropivacaine on the basal spontaneous contractions and contractions induced by various stimuli, namely, KCl (60 mM), carbachol (CCh), and electrical field stimulation (EFS). The effect of local anesthetic agents on Ca(2+)-independent sustained tonic contraction (SuTC) of the detrusor was also investigated. RESULTS: Local anesthetics increased phasic and tonic spontaneous contractile activity dose dependently in the concentration range 1-500 muM, but abolished phasic activity at higher concentrations. Local anesthetic agents inhibited nerve-mediated contraction (EFS, 0.8 msec) in a concentration-dependent manner (ropivacaine > tetracaine = bupivacaine > lidocaine), and inhibited non-nerve mediated contractions induced by KCl, long pulse EFS (direct muscle stimulation, 100 msec), and CCh. Inhibitory potency on non-nerve mediated contraction was for long pulse EFS: ropivacaine = tetracaine > bupivacaine = lidocaine and for KCl- and CCh-induced contractions: ropivacaine > tetracaine > bupivacaine = lidocaine. Higher concentrations of local anesthetics were needed to inhibit non-nerve-mediated bladder contraction than nerve-mediated contraction. SuTC was suppressed by all local anesthetics concentration dependently. CONCLUSIONS: Our study demonstrates that local anesthetics have inhibitory effects on the contraction of human bladder as induced by different stimulants and concentrations. Their effects and differences suggest that they may be considered potentially useful as diagnostic and therapeutic agents for bladder dysfunction.     

Complications in the use of intravenous catheters for major surgery: A clinical study

Two groups of patients received one of two intravenous catheters, a 20-gauge (ga) Criticon (C group;n=96) or a 20-gauge (ga) Vitaflon Plus (V group;n=100). Each catheter was inserted under identical cannulation conditions. Fluids and drugs used pre- and postoperatively were comparable in both groups. All catheters remained in place for a minimum of 4 days. Variables related to the quality of cannula were more favorable with the V group catheter. The incidence of early complications (erythema, swelling, tissue hardness, pain) was comparable in both groups. The survival distribution curves for all complications and swelling >2 cm were significantly longer in the V group. The frequency of swelling correlated with difficulty during vein penetration, slow blood flashback, and damage to the catheter. The incidence of complications following cannulation was high in both groups. The period from catheter insertion to the clinical onset of phlebitis was prolonged in both groups if antiphlebitogenous fluids were used. The incidence of late complications (phlebitis, displacement of the cannulae, etc.) and damage to the catheters was more frequent in the C group. The authors discuss the clinical relevance of these findings.     

Effects of propofol on guinea pig respiratory smooth muscle

The effects of propofol on the tone of guinea pig respiratory smooth muscle was studied both in vitro and in vivo. In vitro, the activity of propofol on tracheal smooth muscle was investigated using a force displacement transducer for isometric tension responses. Isoproterenol was used as the control. Concentration-response curves to propofol and isoproterenol were obtained using a cumulative dose schedule. Propofol (0.32–10.24 μg·ml⁻¹) relaxed the tracheal smooth muscle in a concentration-dependent manner, but was less potent than isoproterenol (equipotent molar ratio 29 000∶1). This effect of propofol was not affected by prior administration of atropine, propranolol, prazocin, or yohimbine, and it did not appear to be mediated via calcium antagonism. The solvent for propofol (10% intralipid) had no effect on the tracheal smooth muscle in vitro. The in vivo study measured the effect of propofol on lung pressure in deeply anesthetized guinea pigs using histamine induced bronchoconstriction. Propofol (1–4.5 mg·kg⁻¹, i.v.) exhibited neither relaxant nor constrictor effects. It is possible that the effects of propofol observed in vitro are due to nonspecific action, while the finding of no effect in vivo could be due to different tissue sensitivity to propofol, i.e., tracheal smooth muscle may be more responsive than bronchial smooth muscle. Propofol does not seem to have any deleterious effects on airway smooth muscle.     

Effects of intracellular MgADP and acidification on the inhibition of cardiac sarcolemmal ATP-sensitive potassium channels by propofol

Purpose Propofol inhibits adenosine triphosphate-sensitive potassium (K_ATP) channels, which may result in the blocking of ischemic preconditioning in the heart. During cardiac ischemia, sarcolemmal K_ATP channel activity is regulated by the increased levels of cytosolic metabolites, such as adenosine diphosphate (ADP) and protons. However, it remains unclear whether these cytosolic metabolites modulate the inhibitory action of propofol. The aim of this study was to investigate the effects of intracellular MgADP and acidification on K_ATP channel inhibition by propofol. Methods We used inside-out patch-clamp configurations to investigate the effects of propofol on the activities of recombinant cardiac sarcolemmal K_ATP channels, which are reassociated by expressed subunits, sulfonylurea receptor (SUR) 2A, and inwardly rectifying potassium channels (Kir6.2). Results In the absence of MgADP, propofol inhibited the SUR2A/Kir6.2 channel currents in a concentration-dependent manner, and an IC₅₀ of 78 μM. Increasing the intracellular MgADP concentrations to 0.1 and 0.3 mM markedly attenuated the inhibitory potency of propofol, and shifted the IC₅₀ to 183 and 265 μM, respectively. Moreover, decreasing the intracellular pH from 7.4 to 6.5 attenuated the inhibitory potency of propofol, and shifted the IC₅₀ to 277 μM. In addition, propofol-induced inhibition of truncated Kir6.2ΔC36 currents, which form a functional channel without SUR2A, was not affected by an increase in intracellular MgADP. However, intracellular acidification (pH 6.5) significantly reduced the propofol sensitivity of Kir6.2ΔC36 channels. Conclusion Our results demonstrated that the existence of intracellular MgADP and protons attenuated the direct inhibitory potency of propofol on recombinant cardiac sarcolemmal K_ATP channels, via SUR2A and Kir6.2 subunits, respectively.     

Impact of propofol on electrocardiographic alterations during intravascular application of bupivacaine--a study in piglets

Background: Intravascular application of a small dose of local anesthetics (LA) with epinephrine as well as larger doses of LA under sevoflurane anesthesia results in increase in T‐wave amplitude in the electrocardiogram (ECG). The aim of this study was to elucidate whether propofol anesthesia affects these ECG alterations or not. Methods: Thirty neonatal pigs were randomized into two groups. Group 1 was anesthetized with sevoflurane, group 2 with sevoflurane plus continuous propofol infusion (10 mg·kg^?1·h^?1). A test dose of 0.2 ml·kg^?1 bupivacaine 0.125% + epinephrine 1 : 200 000 was injected intravenously. Arterial pressure was monitored. ECG was analyzed for changes in T‐wave amplitude (positive if ≥25% baseline) and heart rate. In another setting, bupivacaine 0.125% was intravenous infused at a rate of 4 mg·kg^?1·min^?1. ECG was analyzed for alteration in T‐wave amplitude and heart rate at 1.25, 2.5, and 5 mg·kg^?1 bupivacaine infused. Results: T‐wave elevation after the administration of an epinephrine containing LA test dose was similar between the two groups. Increase in heart rate caused by the test dose were significantly higher in group 2 (P = 0.008). During continuous bupivacaine administration, T‐wave elevation occurred in 40% and 71% (group 1 and 2) at 1.25 mg·kg^?1, in 80% and 100% at 2.5 mg·kg^?1, and in 93% and 86% at 5 mg·kg^?1 bupivacaine infused. Conclusion: Continuous propofol infusion does not suppress the ECG signs of a systemically administered epinephrine containing LA test dose nor does it suppress the ECG signs caused by high doses of intravenous applied bupivacaine.     

Effects of fentanyl or alfentanil as supplement to propofol anaesthesia for termination of pregnancy

One hundred and twenty patients undergoing early legal termination of pregnancy by dilatation and suction curettage before 12 weeks of pregnancy were randomly allocated to receive total intravenous propofol anaesthesia either alone or supplemented with fentanyl 1.5 μg·kg^-1 or alfentanil 15 μg kg^-1. Supplementation with fentanyl or alfentanil improved operating conditions ( P <0.01), reduced total propofol requirements ( P < 0.01) and reduced postoperative pain intensity ( P < 0.05). Immediate recovery, assessed by the time patients took to open the eyes, to give correct date of birth and by co–operation score, was more rapid in the alfentanil group compared to the control group ( P < 0.05), whereas there was no significant difference between the alfentanil and fentanyl groups. The three anaesthetic techniques did not differ with regard to side effects.
In conclusion, total intravenous propofol anaesthesia in patients undergoing early termination of pregnancy was improved by supplementation with either fentanyl 1.5 μg kg^-1 or alfentanil 15 μg–kg^-1. The benefit was slightly greater with alfentanil than with fentanyl.     

Effects of propofol on isolated human pial arteries

BACKGROUND: The intravenous anaesthetic propofol has been reported to increase cerebral vascular resistance in vivo. The underlying mechanisms are not fully understood, but may include effects on metabolism and direct effects on the vascular smooth muscle. The present study was designed to evaluate the direct effects of propofol on human pial arteries. METHODS: We investigated the direct effect of propofol (10(-6)-10(-4) M) on isolated human pial arteries at basal tension as well as the influence on contractions induced by 5-hydroxytryptamine, prostaglandin F2alpha, noradrenaline and potassium chloride. RESULTS: Propofol did not change the basal tension. Propofol at 10(-6) and 10(-5) M did not affect the concentration-response curves of any of the contractile agents tested. Propofol at the supraclinical concentration 10(-4) M reduced the contractions induced by all contractile agents. CONCLUSION: Propofol reduces the tone of human pial arteries in vitro at supraclinical concentrations, but has no effect on the tone at clinically relevant concentrations.     

Effects of propofol on cerebral blood flow and the metabolic rate of oxygen in humans

BACKGROUND: Effects of propofol on human cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and blood flow-metabolism coupling have not been fully evaluated. We therefore assessed the effects of propofol on total-CBF and CMRO2 in patients without noxious stimuli and neurologic disorders. METHODS: General anesthesia was induced with midazolam (0.2 mg/kg) and fentanyl (5 microg/kg) in 10 patients (ASA physical status I) undergoing knee joint endoscopic surgery. Epidural anesthesia was also performed to avoid noxious stimuli during surgery. Cerebral blood flow (CBF) and cerebral arteriovenous oxygen content difference (a-vDO2) was measured using the Kety-Schmidt method with 15% N2O as a tracer before and after propofol infusion (6 mg/kg/h for 40 min), and the CMRO2 was also calculated. RESULTS: CBF decreased following propofol infusion from 34.4 ml/100 g/min (range 28.4-52.0) to 30.0 ml/100 g/min (range 20.2-42.4) (P=0.04). Although there was no significant change in a-vDO2, CMRO2 decreased following propofol infusion from 2.7 ml/100 g/min (range 2.2-4.3) to 2.2 ml/100 g/min (range 1.4-3.0) (P=0.04). There was a strong linear correlation between CBF and CMRO2 (r=0.90). CONCLUSION: Propofol proportionally decreased CBF and CMRO2 without affecting a-vDO2 in humans, suggesting that normal cerebral circulation and metabolism are maintained.     

Mechanisms of direct inhibitory action of propofol on uterine smooth muscle contraction in pregnant rats.

BACKGROUND: Although propofol directly inhibits uterine smooth muscle contraction, the mechanisms of this effect are still unknown. The current study aimed to clarify the mechanisms of the inhibitory effect of propofol on oxytocin-induced uterine smooth muscle contraction by measuring (1) the concentration of intracellular free Ca(2+) ([Ca(2+)](i)) simultaneously with muscle tension, (2) the amount of intracellular inositol 1,4,5-triphosphate ([IP(3)](i)), and (3) voltage-dependent Ca(2+) channel (VDCC) activity. METHODS: Uterine smooth muscle tissues were obtained from pregnant rats (in late gestation). [Ca(2+)](i) with isometric tension was monitored by the 500-nm light emission ratio of preloaded Ca(2+) indicator fura-2. [IP(3)](i) and VDCC activity were measured by radioimmunoassay and patch clamp techniques, respectively. The uterine smooth muscle was stimulated by 20 nm oxytocin and exposed to propofol (10(-7) approximately 10(-4) m). RESULTS: Propofol had significant inhibitory effects on oxytocin-induced uterine smooth muscle contraction and increased [Ca(2+)](i) in pregnant rats in a dose-dependent manner, without affecting the agonist-receptor binding affinity. Propofol inhibited the increase in [IP(3)](i) induced by oxytocin. Propofol also inhibited VDCC activity in both activated and inactivated states. The solvent Intralipid had no effects on these parameters. CONCLUSIONS: Propofol inhibits oxytocin-induced uterine smooth muscle contraction, at least in part, by decreasing [Ca(2+)](i) without affecting agonist-receptor binding; the inhibitory effect of propofol on [Ca(2+)](i) might be mediated both by a decrease in [IP(3)](i) and by inhibition of VDCC activity.     

Effects of cyproterone acetate on the ultrastructure of the human epididymis

Summary. The effects of cyproterone acetate (CPA), an antiandrogenic steroid, on the ultrastructure of the epithelial cells of the human epididymis were studied. Alterations in the cell size, in the cytoplasmic and surface characteristics, and in the morphology of different organelles are described.
The different ultrastructural changes observed suggest that the absorptive and secretory functions of the principal cells are impaired following the CPA treatment. By contrast, with the drastic response of the principal cells of the ductuli efferentes and caput epididymidis, the epithelial cells of the cauda epididymidis appeared less affected. The suggestion of a differential androgen dependence among the different regions of this androgen target organ, as well as between the major cell-types of the epididymal epithelium, is briefly discussed.